New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment

Peter Kruzliak,Olga Pechanova,Tomas Kara

doi:10.1007/s10741-013-9397-4

Abstract

Nitric oxide (NO) is often used to treat heart failure accompanied with pulmonary edema. According to present knowledge, however, NO donors are contraindicated when systolic blood pressure is less than 90 mmHg. Based on recent findings and our own clinical experience, we formulated a hypothesis about the new breakthrough complex lifesaving effects of NO donors in patients with cardiac arrest and cardiopulmonary resuscitation therapy. It includes a direct hemodynamic effect of NO donors mediated through vasodilation of coronary arteries in cooperation with improvement of cardiac function and cardiac output through reversible inhibition of mitochondrial complex I and mitochondrial NO synthase, followed by reduction in reactive oxygen species and correction of myocardial stunning. Simultaneously, an increase in vascular sensitivity to sympathetic stimulation could lead to an increase in diastolic blood pressure. Confirmation of this hypothesis in clinical practice would mean a milestone in the treatment for cardiac arrest and cardiopulmonary resuscitation.

Highlights

Research of over two decades has shown nitric oxide (NO) to be a ubiquitous modulator of biological phenomena from cell signal to effector and from physiology to pathophysiology
All four NO synthase (NOS) isoforms - endothelial NOS, neuronal NOS, inducible NOS and mitochondrial NOS - have been shown to be present in the human myocardium and may be activated in response to hypoxia or ischemia
These results, along with other studies, have defined Nitric oxide (NO) as a dual-faced molecule in IR injury, which contributes to both cardioprotective and deleterious signaling pathways within the myocardium. In this regard, understanding how to deliver NO may facilitate beneficial therapeutic exploitation of NO signaling in IR injury, while minimizing the deleterious effects of NO. With respect to these experimental results, it seems to indicate that the protective effects of low-dose nitric oxide in the whole heart are not mediated by their generation, which appears contrary to a previous report using exogenous nitric oxide used as a trigger of preconditioning [83] and postconditioning

Summary

Introduction

Research of over two decades has shown nitric oxide (NO) to be a ubiquitous modulator of biological phenomena from cell signal to effector and from physiology to pathophysiology. It includes a direct hemodynamic effect of NO donors mediated through vasodilation of coronary arteries in cooperation with improvement of cardiac function and cardiac output through reversible inhibition of mitochondrial complex I and mitochondrial NO synthase, followed by reduction in reactive oxygen species and correction of myocardial stunning.

Results

Conclusion